Serum biomarkers are used for diagnosis of disease and for predicting and monitoring response to treatment (Sidransky, D. 2002. Nat Rev Cancer 2:210-219; Bidart, J. M., et al. 1999. Clin Chem 45:1695-1707). Most clinically useful markers, to date, have been plasma proteins that require individual immunoassays for quantitation (Jortani, S. A., et al. 2004. Clin Chem 50:265-278; Watts, N. B. 1999. Clin Chem 45:1359-1368). Human serum also contains smaller peptides that constitute an entity known as the serum ‘peptidome’. Advances in mass spectrometry (MS) now permit the display of hundreds of small to medium sized peptides from microliter volumes of serum (Koomen, J. M., et al., 2005. J Proteome Res 4:972-981; Villanueva, et al., 2004. Anal Chem 76:1560-1570). Several recent reports have advocated the use of MS-based serum peptide profiling to determine qualitative and quantitative patterns, or ‘signatures’, that indicate the presence/absence of disease such as cancer (Petricoin, E. F., et al., 2002. Lancet 359:572-577; Adam, B. L., et al., 2002. Cancer Res 62:3609-3614; Li, J., et al., 2002. Clin Chem 48:1296-1304; Ebert, M. P., et al., 2004. J Proteome Res 3:1261-1266; Ornstein, D. K., et al. 2004. J Urol 172:1302-1305; Conrads, T. P., et al., 2004. Endocr Relat Cancer 11:163-178). To date, it has neither been accomplished to independently reproduce entire peptidomic patterns, nor has it been shown that the highly discriminatory peptides have the same amino acid sequences.
TOF-MS is the most efficient mass analysis technique in terms of detection sensitivity and readily achieves high mass analysis at good mass accuracy (R. J. Cotter, Anal. Chem. 64 (21), 1027 (1992)). It is one of the few analysis techniques that combines high sensitivity, selectivity and specificity with speed of analysis. For example, TOF-MS can record a complete mass spectrum on a microsecond timescale.
Advances in MS-based serum peptide profiling can have important implications for cancer diagnostics.